Anti-CD19 CAR-T cell therapy for Systemic Lupus Erythematosus in a mouse disease model

Abstract

Abstract Dysregulated B cell activation plays pivotal roles in systemic lupus erythematosus (SLE), which makes B-cell-depletion a potential strategy for SLE treatment. The clinical success of anti-CD19 chimeric antigen receptor (CAR) T cells in treating B-cell malignancies has attracted the attention of researchers. In this study, we aimed to investigate the feasibility of applying anti-CD19 CAR-T cell therapy into SLE treatment in a mouse disease model. We have constructed murine anti-CD19 CARs with either CD28 or 4-1BB as the intracellular costimulatory motif and evaluated the therapeutic functions of corresponding CAR-T cells by infusing them into MRL-lpr mice. We found that adoptive transfer of anti-CD19 CAR-T cells was able to achieve sustained B-cell-depletion in MRL-lpr mice. More importantly, transferring syngeneic anti-CD19 CAR-T cells can not only prevent disease pathogenesis before the onset of disease symptoms but also have substantial therapeutic benefits in disease treatment at a later stage after disease progression. Comparing to CAR-T cells with CD28 as a costimulatory motif, CAR-T cells with 4-1BB costimulatory motif work better for mouse SLE treatment. In summary, our study claimed that anti-CD19 CAR-T cell therapy worked effectively in treating murine SLE, indicating its potential in treating human patients in clinic.